PHARMACOLOGICAL STUDIES OF STONEFISH (SYNANCEJA-TRACHYNIS) VENOM

The present study was designed to examine some of the pharmacological properties of venom from the stonefish (Synanceja trachynis), with particular reference to the presence in the venom of pain-producing/enhancing substances. Stonefish venom (1-6 mu g/ml) produced concentration-dependent contractile responses in guinea-pig isolated ileum. No tachyphylaxis, or reduction in responses with time, was observed to venom (3 mu g/ml) in ileum. The response to venom (3 mu g/ml) was not significantly affected by the histamine antagonist mepyramine (0.5 mu M), or a preceding anaphylactic response. Mecamylamine, 5HT-desensitization or EXP3174 failed to have any significant effect on responses to venom (3 mu g/ml), suggesting that the venom does not have action at ganglionic nicotine, 5HT or angiotensin II receptors, respectively. Prior incubation with blood acetylcholinesterase did not significantly inhibit responses to venom (3 mu g/ml). Responses to venom (3 mu g/ml) were significantly inhibited by the cyclooxygenase inhibitor indomethacin (5 mu M), the leukotriene D-4 receptor antagonist FPL55712 (1 mu M), the thromboxane A(2) receptor antagonist GR32191B (1 mu M), the muscarinic receptor antagonist atropine (10 nM) and the neurokinin-1 receptor antagonist CP96345 (0.1 mu M). Venom (6 mu g/ml) produced contractile responses in the rat isolated vas deferens which were abolished by the alpha(1)-adrenoceptor antagonist prazosin (0.3 mu M) and significantly potentiated by the neuronal uptake inhibitor DMI (1 mu M). However, noradrenergic transmitter depletion with reserpine (5 mg/kg, i.p.) did not significantly inhibit responses to venom (6 mu g/ml). Histamine fluorometric and phospholipase A(2) assays failed to detect significant quantities of either substance in the venom. These results suggest that stonefish venom may cause the release of acetylcholine, substance P, and cyclooxygenase products, or contain components which act at these receptors. The venom also appears to contain a component which is a substrate for neuronal uptake and has a direct action at alpha(1)-adrenoceptors.